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Antimicrobial Agents and Chemotherapy, January 2007, p. 239-244, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00762-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Voriconazole Concentration in Human Aqueous Humor and Plasma during Topical or Combined Topical and Systemic Administration for Fungal Keratitis{triangledown}

Michael A. Thiel,1,{dagger} Annelies S. Zinkernagel,2,{dagger}* Jürgen Burhenne,3 Claude Kaufmann,1 and Walter E. Haefeli3

Department of Ophthalmology, University of Zurich, Zurich, Switzerland,1 Division of Infectious Diseases and Hospital Epidemiology, Department of Internal Medicine, University of Zurich, Zurich, Switzerland,2 Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany3

Received 22 June 2006/ Returned for modification 15 August 2006/ Accepted 15 October 2006

Voriconazole (VRC) is an antifungal drug that effectively treats keratitis caused by yeasts and molds when administered orally. We retrospectively evaluated clinical outcomes and plasma and aqueous humor drug concentrations in five patients with fungal keratitis and one patient with posttraumatic endophthalmitis who were treated with VRC. VRC was administered either topically (1% eye drops every hour) or orally (400 mg twice a day). Plasma and aqueous humor samples from affected eyes were taken 12 h after oral administration or 1 h after eye drop application. The drug concentration was measured by liquid chromatography with UV or mass spectrometric detection. All six patients responded well to VRC treatment. The VRC concentration ranged from 2.93 to 3.40 mg/liter in the aqueous humor and from 3.20 to 4.20 mg/liter in the plasma after combined oral and topical treatment. Topical administration alone resulted in highly variable trough VRC concentrations of 0.61 to 3.30 mg/liter in the aqueous humor. VRC concentrations were above the MIC for Candida albicans Aspergillus fumigatus and clinical improvement was seen in all four patients with C. albicans and A. fumigatus keratitis. Combined orally and topically administered VRC resulted in aqueous humor drug concentrations of ≥2.93 mg/liter, which is above the VRC MIC for most fungi. Topical VRC treatment resulted in an aqueous humor drug concentration >0.61 mg/liter, which is above the MIC for most Candida species. The results from this small series of patients suggest that both topical and combined systemic and topical VRC therapy can be effective in treating fungal keratitis. Furthermore, the data provide preliminary support for initiation of VRC treatment with a combined topical and systemic administration until the causative fungus and its MIC are identified.

* Corresponding author. Present address: Division of Pediatric Infectious Diseases, UCSD School of Medicine, Cellular & Molecular Medicine East, Room 1088, 9500 Gilman Drive, Mail Code 0687, La Jolla, CA 92093-0687. Phone: (858) 534-9760. Fax: (858) 534-5611. E-mail: azinkernagel{at}ucsd.edu.

{triangledown} Published ahead of print on 23 October 2006.

{dagger} M.A.T. and A.S.Z. contributed equally.

Antimicrobial Agents and Chemotherapy, January 2007, p. 239-244, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00762-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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